Different Modes Of Administration Research Articles

Tapering Biologic Therapy for Rheumatoid Arthritis: A Qualitative Study of Patient Perspectives.

Biologic therapies are cost effective for active rheumatoid arthritis but have adverse effects and are costly. Tapering of biologics is emerging as an important consideration when sustained remission is achieved. Recent trials have highlighted the clinical feasibility of tapering, but there is little evidence on how proposed tapering would be received by patients. The aim of this study was to explore factors influencing hypothetical decisions of patients with rheumatoid arthritis on tapering their biologics and their perspectives on remission and flare when considering the possibility of tapering. Patients with rheumatoid arthritis with diverse experiences of biologics with different modes of administration were purposively sampled to participate in one of six focus groups (n = 43) or an individual interview (n = 2). Transcripts were analyzed using inductive thematic analysis. Five overarching themes on what influences a participant's decision to taper their biologic were identified. First, participants were fearful of uncertain outcomes of tapering, especially flare and joint damage. Second, participants prioritized quality of life from continuing biologics over the risk of adverse effects. Third, tapering biologics was seen as providing relief from the inconvenience of taking biologics regularly. Fourth, participants wanted assurance of prompt access to healthcare if their rheumatoid arthritis were to flare when tapering. Fifth, preferences for involvement in decision making varied, but fulfilling information needs was desired to aid a patient's preferred role in decision making on tapering. This study provides novel insight into the perspectives of patients with rheumatoid arthritis on tapering biologics when sustained remission is achieved at a crucial juncture in global affordability for healthcare systems. These patient perspectives can inform the planning of decision aids and clinical trials of decision-making processes when tapering is proposed.

Efficacy of local and systemic corticosteroid and hyaluronidase therapy in oral submucous fibrosis: a histopathological study

<p class="abstract"><strong>Background:</strong> As the etiopathogenesis of OSMF is not well established, a myriad of different medical and surgical modalities of treatment are reported however studies on histopatholgical changes after treatment are very sparse. There are reports on various regimens of steroids using different molecules, doses and routes of administration and their combination with other drugs. These were the driving factors to conduct this study. This histopathological study was conducted to know the efficacy of various forms of steroid therapy in various combinations.</p><p class="abstract"><strong>Methods:</strong> This prospective randomized single blinded outcome based study was conducted in the department of Otorhinolaryngology (ENT) and Pathology in a tertiary care medical college hospital. The 150 clinically diagnosed patients were divided into 5 groups: A, B, C, D and E. Each group was treated differently with different modes of administration of steroids with and without combinations of other medicines. To study histopathological changes before and after treatment, biopsy was taken in 100 patients who gave their consent for the same. </p><p class="abstract"><strong>Results:</strong> The various histopathological changes observed in the tissues taken after the treatment in 100 patients, were in terms of changes in the epithelium towards normalisation, decrease in fibrous tissue in the submucosa, decrease in the cellular infiltration, appearance of new capillaries, restoration of glandular activity and decrease in the fibrosis of muscles. The calculated Chi square value (p>0.05) was found less than table value.</p><p class="abstract"><strong>Conclusions: </strong>Local and systemic corticosteroid and hyaluronidase therapy<strong> </strong>in patients with OSMF<strong> </strong>were found effective. However, histopathologically, it was not found statistically significant whether corticosteroids are given locally and/or systemic with or without injection hyaluronidase.</p>

Cardioprotective activity and screening of N-substituted of quinazolin-4(3Н)-ones

Cardioprotection is a promising direction of therapy for myocardial infarction and the search for new substances with cardioprotective properties remains an urgent task in pharmacology. N -substituted quinazolin-4(3H)-ones, which are characterized by antihypoxic, antioxidant, angioprotective, anti-inflammatory, and others properties may have the cardioprotective activity. The purpose of the study is to detect the presence and the degree of cardioprotective effect in a number of N -substituted quinazolin-4(3H)-ones in the model of acute experimental myocardial infarction in different modes of administration, to determine a “structure – action” dependence, to identify a leader compound promising for in-depth study of its pharmacological properties. Materials and methods. 300 non-linear rats of both sexes, weighing 180–220 g, were used in this study. Myocardial infarction was modeled by diathermocoagulation of the coronary artery. In the 1st series of experiments, the studied substances and reference drugs amiodarone, mexidol and thiotriazoline were administered in the prophylactic, and in the 2nd series – in the therapeutic regimen. The cardioprotective effect size was estimated on the basis of the mortality rate of animals. Results . The cardioprotective activity of both the test compounds and reference drugs was evidenced by a decrease in the mortality rate of animals with a heart attack in the critical periods of the experiment relative to the control. The PC-66 has been found to be the most effective: the mortality rate was 20 % versus 54 % of the control in the critical period of the experiment, that is, it was 2.7 times less than in the control. The test substances by the degree of cardioprotective effect in the course of therapeutic introduction into the body can be arranged in the following order: PC-66 = amiodarone ≥ mexidol ≥ thiotriazoline> PC-32 = PC-51. Cardioprotection, the signs of which were found in the PC-66 compound, are well combined with the presence of central analgesic and cerebroprotective effects, which suggests the multifactorial effects of this substance. We can state the originality of the resulting substance and its potential properties. Conclusions. N -substituted quinazolin-4(3H)-ones exhibit cardioprotective activity. 4-(4-oxo-4H-quinazolin-3-yl) benzoic acid (compound PC-66) displays cardioprotective properties the most. The obtained data testify to the prospects of the pharmacological properties and safety of the PC-66 compound in-depth study.

Ethnobotanical and Ethnomedicinal Studies of Salher and Mulher Forest from District Nashik (Maharashtra)

Herbs are an integral part of variety of cultures in India and have been used over centuries. The aim of this study is to document the Ethnobotanical plants from Salher and Mulher and its adjoining areas and to collect information regarding various uses of plants. The area is near to famous Dang forest of Gujarat. It is a representative area from Western Ghats of Maharashtra. The forest area comprises a rich biosphere ranging from thick evergreen forest to heavily eroded barren hills. The survey was conducted during the period July 2017 to October 2018. Information was gathered from native tribes of this region namely Bhil, Kokana and Mahadeo koli. These tribes use herbal medicine as a primary mode of health care. A total 33 species belonging to 31 genera and 28 families have been documented in this study. The medicinal plants used by Bhil and Kokana are listed with botanical name, family, local name and their ethnomedical uses. It was observed that the documented ethnomedicinal plants were mostly used to cure skin diseases, stomach disorders, jaundice, poison bites, impotency etc. The tribal people use different modes of administration of drugs like kadhas (decoction), bhasmas (ash), paste, poultice, powder, infusion etc. The knowledge about these practices has been handed over from one generation to other but it now faces the danger of getting lost with passing years. So, it is necessary to identify and document these species for their conservation and sustainable utilization. These studies will also provide new material for workers in the field of Phytochemistry and Pharmacology. Key words: Ethnobotanical, Herbal drug, Salher and Mulher

Étude Ethnobotanique et Screening Phytochimique de Quelques Ptéridophytes de la Forêt Classée de Yapo-Abbé (Côte d’Ivoire)

An ethnobotanical study with phytochemical screening of some Pteridophytes was carried out in the classified forest of Yapo-Abbé in the south of Côte d'Ivoire, in the Agboville Department, precisely in the subprefecture of Azaguié. The objective of this study was to show the different uses of the Pteridophytes of this forest. The approach method is an ethnobotanical survey carried out among the populations of the study area. This survey consisted in drafting a questionnaire beforehand to apprehend the multiple uses of Pteridophytes among the surrounding population and to develop a photo album of Pteridophytes to be presented during the interview. The data collection was carried out using the semi-structured interview method and with the help of an interpreter guide. It identified 19 species of Pteridophytes including six (6) species used as medicinal plants. No other use of these taxa was mentioned. The whole plant is the most solicited or 73.33% for the preparation of medicinal recipes. Various methods of preparation such as decoction (33.3%), kneading (33.3%), softening (20%) and use in the fresh state (13.3%) are used for recipes. single species. There are also different modes of administration of phytomedicaments: drink (42.85%), local application (37.71%), mastication (7.14%) and massage (7.14%). The phytochemical sorting performed on the hydroethanolic extracts revealed that the different drugs of these plants contain sterols, polyterpenes, polyphenols, European Scientific Journal November 2018 edition Vol.14, No.33 ISSN: 1857 – 7881 (Print) e - ISSN 1857- 7431 174 flavonoids, catechin tannins, alkaloids and quinones which give them various therapeutic properties.

A novel approach to devise the therapy for ventricular fibrillation by epicardial delivery of lidocaine using active hydraulic ventricular attaching support system: An experimental study in rats.

Active hydraulic ventricular attaching support system (ASD) placed around the heart is not only a novel, nontransplant surgical device used for epicardial administration of drugs like lidocaine, but also a promising treatment option for ventricular fibrillation (VF) and arrhythmias. We hypothesize that lidocaine in 5 mg/kg dose released by ASD significantly improves the VF in the rat model. Sprague-Dawley (SD) rats were selected and were divided into four groups, intravenous injection (IV), epicardial infusion (EI), ASD, and control. ASD group was further divided into four subgroups for different lidocaine doses (i) ASD+A group (10 mg/kg), (ii) ASD+B group (5 mg/kg), (iii) ASD+C group (1 mg/kg), and (iv) ASD+D group (0.1 mg/kg). VF was induced with calcium chloride injection and was confirmed by electrocardiogram (ECG) in all the groups. VF was treated with different doses of lidocaine using different modes of administration. Data were analyzed using the SPSS 19.0 Chi-square tests and one-way analysis of variance (ANOVA). The Kaplan-Meier curve for OS was compared to the Logrank test based on the survival time. P < 0.05 was considered as statistically significant. ASD + B group (5 mg/kg) showed significantly reduced sgroup. The time of first sinus rhythm recovered (15.96 ± 21.77 min) and ▵T-SOD in plasma (-42.02 ± 26.99 U/mL) was significantly different than that of control, IV, and EI groups. ▵T-SOD in plasma for all ASD-treated groups was smaller than the control and IV groups. This study proves that ASD with 5 mg/kg lidocaine dose appears as a promising therapeutic platform for treating VF in rats. Furthermore, ASD may also have potential for treating VF or other cardiovascular disease with different therapeutic agents. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1722-1731, 2019.

The antiulcer effect of the thick water-alcohol extract from unripe walnut fruits on the model of acute alcohol-prednisolone ulcer of the rat’s stomach in different modes of administration

The importance of herbal medicines cannot be overestimated. The presence of the walnut nut in the composition of BAS causes a large number of pharmacological effects, such as anti-inflammatory, antioxidant, membrane- stabilizing, reparative, softening, astringent and antimicrobial, and it makes a thick extract of unripe walnut fruits a promising remedy for the treatment or prevention of stomach ulcer. Aim. To study the antiulcer activity of a thick extract from unripe walnut fruits in different modes of administration on the model of alcohol-prednisolone ulcer in rats. Materials and methods. The study object is a thick water-alcohol (30 % ethanol) extract from unripe walnut fruits (EIWF 30). The antiulcer properties of EIWF 30 were studied on the alcohol-prednisolone model of experimental ulcers. The thick extract was administered in preventive, curative, therapeutic and prophylactic modes intragastrically in the dose of 25 mg/kg. The intensity of ulcerative lesions and the antiulcer activity was assessed by macroscopic indices of the intensity of ulcerative defects in the coolant. Gastrointestinal parameters and the coolant state were evaluated. Results. The antiulcer activity of EIWF 30 in the dose of 25 mg/kg on the alcohol-prednisolone gastric ulcer in rats in the preventive mode of administration exceeds the activity of the reference drug by 16.67 %, in the therapeutic mode by 15.30 %, in the therapeutic and prophylactic mode by 15.38 %. The results obtained confirm the morphological studies. The administration of EIWF 30 in the dose of 25 mg/kg in the therapeutic and prophylactic mode contributed to a significant improvement in the state of the gastric mucosa structures, ulcerous lesions were absent, and the histological pattern corresponded to a mildly expressed reactive gastritis. Conclusions. The introduction of the alcohol-prednisolone mixture led to development of acute ulcerative lesions of the stomach as evidenced by the data from the macroscopic study of the coolant. EIWF 30 in the dose of 25 mg/kg for this pathology in various modes of administration shows the antiulcer activity, which is not inferior to the activity of the reference drug.

Elicitation of health state utilities associated with the mode of administration of drugs acting on the prostacyclin pathway in pulmonary arterial hypertension

IntroductionPulmonary arterial hypertension (PAH) is a rare, incurable disease associated with decreased life expectancy and a marked impact on quality of life (QoL). There are three classes of drugs available for treatment: endothelin receptor antagonists (ERA), drugs acting on nitric oxide pathway (riociguat and phosphodiesterase type 5 inhibitors [PDE5i]), and drugs acting on prostacyclin pathway. The latter have widely different modes of administration – continuous intravenous infusion, continuous subcutaneous infusion, inhaled, and oral – each associated with variable treatment burden, and implications for health economic assessment. This study aimed to establish utility values associated with different modes of administration of drugs acting on the prostacyclin pathway for use in economic evaluations of PAH treatments.MethodsA UK general public sample completed the EQ-5D-5L and valued four health states in time trade-off interviews. The health states drafted from literature and interviews with PAH experts (n=3) contained identical descriptions of PAH and ERA/PDE5i treatment, but differed in description of administration including oral (tablets), inhaled (nebulizer), continuous subcutaneous infusion, and continuous intravenous infusion.ResultsA total of 150 participants (63% female; mean age 37 years) completed interviews. Utilities are presented as values between 0 and 1, with 0 representing the state of being dead and 1 representing being in full health. The mean (SD) utility for oral health state was 0.85 (0.16), while all other health states were significantly lower at 0.74 (0.27) for inhaled (p=0.001), 0.59 (0.31) for subcutaneous (p<0.001) and 0.54 (0.32) for intravenous (p<0.001), indicating that there are disutilities (negative differences) associated with non-oral health states. Disutilities were −0.11 for inhaled, −0.26 for subcutaneous, and −0.31 for intravenous administration.ConclusionThe results demonstrate quantifiable QoL differences between modes of administration of drugs acting on the prostacyclin pathway. QoL burden should be considered for economic evaluation of drugs for PAH treatment.

065 A pilot time and motion study for treatments of relapsing remitting multiple sclerosis (RRMS) in australia

IntroductionThe time burden of managing relapsing remitting multiple sclerosis (RRMS) for patients and healthcare staff is not well quantified despite its importance in treatment choice. Of interest were three higher efficacy RRMS therapies, cladribine tablets, alemtuzumab, and fingolimod because of their different modes of administration. Time and motion (T and M) surveys have previously been used to quantify time burden by asking respondents about duration of treatment administration. The objective is to determine the time taken by patients, nurses, neurologist and other specialists to treat RRMS with cladribine tablets, alemtuzumab and fingolimod using purposely developed T and M surveys.MethodsWe created two T and M surveys, one for neurologists and nurses, and another for patients. Surveys were informed by product information documents, validated by an MS nurse, and completed by telephone with patients (n=3), neurologists (n=3), and nurses (n=8) from eight MS clinics.ResultsThe overall mean time spent on treatment with cladribine tablets, fingolimod, and alemtuzumab extrapolated over 4 years was 25±3, 62±6, and 189±18 hours (p&lt;0.0001, 1-way ANOVA, repeated measures). Neurologists’ overall time spent also favoured cladribine tablets (2.3±0.7 hours) over alemtuzumab (9.5±1.8 hours) and fingolimod (2.9±0.7 hours), (overall p=0.001). Similar results were found for nurses and patients, with the largest difference between therapies (favouring cladribine tablets) recorded for patients.ConclusionCladribine tablets were associated with a significantly lower overall time taken to treat RRMS compared to fingolimod and alemtuzumab. This warrants further research to determine if cladribine tablets could (a) increase productivity for doctors and nurses, and (b) improve patient quality of life by reducing the burden of managing their disease.

Pharmacokinetic and pharmacodynamic study of intranasal and intravenous dexmedetomidine

BackgroundIntranasal dexmedetomidine produces safe, effective sedation in children and adults. It may be administered by drops from a syringe or by nasal mucosal atomisation (MAD NasalTM). MethodsThis prospective, three-period, crossover, double-blind study compared the pharmacokinetic (PK) and pharmacodynamic (PD) profile of i.v. administration with these two different modes of administration. In each session each subject received 1 μg kg−1 dexmedetomidine, either i.v., intranasal with the atomiser or intranasal by drops. Dexmedetomidine plasma concentration and Ramsay sedation score were used for PK/PD modelling by NONMEM. ResultsThe i.v. route had a significantly faster onset (15 min, 95% CI 15–20 min) compared to intranasal routes by atomiser (47.5 min, 95% CI 25–135 min), and by drops (60 min, 95%CI 30–75 min), (P<0.001). There was no significant difference in sedation duration across the three treatment groups (P=0.88) nor in the median onset time between the two modes of intranasal administration (P=0.94). A 2-compartment disposition model, with transit intranasal absorption and clearance driven by cardiac output using the well-stirred liver model, was the final PK model. Intranasal bioavailability was estimated to be 40.6% (95% CI 34.7–54.4%) and 40.7% (95% CI 36.5–53.2%) for atomisation and drops respectively. Sedation score was modelled via a sigmoidal Emax model driven by an effect compartment. The effect compartment had an equilibration half time 3.3 (95% CI 1.8–4.7) min−1, and the EC50 was estimated to be 903 (95% CI 450–2344) pg ml−1. ConclusionsThere is no difference in bioavailability with atomisation or nasal drops. A similar degree of sedation can be achieved by either method. Clinical trial registrationHKUCTR-1617.

Second-Hand Exposure of Staff Administering Vaporised Cannabinoid Products to Patients in a Hospital Setting.

BackgroundIn many health settings, administration of medicinal cannabis poses significant implementation barriers including drug storage and safety for administering staff and surrounding patients. Different modes of administration also provide different yet potentially significant issues. One route that has become of clinical interest owing to the rapid onset of action and patient control of the inhaled amount (via breath timing and depth) is that of vaporisation of cannabinoid products. Although requiring a registered therapeutic device for administration, this is a relatively safe method of intrapulmonary administration that may be particularly useful for patients with difficulty swallowing, and for those in whom higher concentrations of cannabinoids are needed quickly. A particular concern expressed to researchers undertaking clinical trials in the hospital is that other patients, nurses, and clinical or research staff may be exposed to second-hand vapours in the course of administering vaporised products to patients.ObjectiveThe objective of this study was to take samples from two research staff involved in administering vaporised Δ9-tetrahydrocannabinol to participants in a clinical trial, to examine and quantitate cannabinoid presence.MethodsBlood samples from two research staff were taken during the exposure period for three participants (cannabis users) over the course of approximately 2.5 h and analysed using tandem mass spectrometry.ResultsBlood samples taken over a vaporised period revealed exposure below the limit of detection for Δ9-tetrahydrocannabinol and two metabolites, using tandem mass spectrometry analytical methods.ConclusionsThese results are reassuring for hospital and clinical trial practices with staff administering vaporised cannabinoid products, and helpful to ethics committees wishing to quantify risk.

Cannabis in Parkinson's Disease: Hype or help?

Cannabis buds and extracts as well as synthetic cannabinoids have been available on prescription to patients with severe diseases since March 2017, with the costs covered by health insurance companies.The prescription of medical marihuana is not restricted to specific symptoms and is therefore also valid for patients with Parkinson's disease. From a legal perspective, patients who are seriously ill even have the right to be treated with cannabis if standard treatment methods are unsuccessful or result in unbearable side effects. This also applies even if only a slight chance of noticeable improvement is predicted as a result of the cannabis treatment.Bearing this in mind and due to an intense media coverage of this topic, more and more patients with Parkinson's disease are requesting cannabis prescription, which is a challenging situation to their neurologists.This article provides an overview of the various cannabis products that can be prescribed, the different modes of administration and the available literature regarding motor- and non-motor symptoms in Parkinson's disease. Furthermore, the authors state their opinion on which indications cannabinoids could be useful in treating patients with Parkinson's disease or in which situation the patient could or even should be prescribed cannabinoids. Additionally, this article presents practical recommendations for the prescription of cannabinoids and patient counseling, e. g., on the effects of medical marijuana on driving capacity.

Pharmacokinetics of Fentanyl and Its Derivatives in Children: A Comprehensive Review.

Fentanyl and its derivatives sufentanil, alfentanil, and remifentanil are potent opioids. A comprehensive review of the use of fentanyl and its derivatives in the pediatric population was performed using the National Library of Medicine PubMed. Studies were included if they contained original pharmacokinetic parameters or models using established routes of administration in patients younger than 18years of age. Of 372 retrieved articles, 44 eligible pharmacokinetic studies contained data of 821 patients younger than 18years of age, including more than 46 preterm infants, 64 full-term neonates, 115 infants/toddlers, 188 children, and 28 adolescents. Underlying diagnoses included congenital heart and pulmonary disease and abdominal disorders. Routes of drug administration were intravenous, epidural, oral-transmucosal, intranasal, and transdermal. Despite extensive use in daily clinical practice, few studies have been performed. Preterm and term infants have lower clearance and protein binding. Pharmacokinetics was not altered by chronic renal or hepatic disease. Analyses of the pooled individual patients' data revealed that clearance maturation relating to body weight could be best described by the Hill function for sufentanil (R 2=0.71, B max 876mL/min, K 50 16.3kg) and alfentanil (R 2=0.70, B max (fixed) 420mL/min, K 50 28kg). The allometric exponent for estimation of clearance of sufentanil was 0.99 and 0.75 for alfentanil clearance. Maturation of remifentanil clearance was described by linear regression to bodyweight (R 2=0.69). The allometric exponent for estimation of remifentanil clearance was 0.76. For fentanyl, linear regression showed only a weak correlation between clearance and bodyweight in preterm and term neonates (R 2=0.22) owing to a lack of data in older age groups. A large heterogeneity regarding study design, clinical setting, drug administration, laboratory assays, and pharmacokinetic estimation was observed between studies introducing bias into the analyses performed in this review. A limitation of this review is that pharmacokinetic data, based on different modes of administration, dosing schemes, and parameter estimation methods, were combined.

Using Patient-Reported Measures in Dialysis Clinics.

Patient-reported outcome measures (PROMs), including patient-reported outcomes (PROs), are one of two primary sources of data about patients on dialysis ([1][1]); the other is biologically based patient data. The Food and Drug Administration definition of a PRO is “any report coming from patients

Evaluating CollaboRATE in a clinical setting: analysis of mode effects on scores, response rates and costs of data collection

BackgroundShared decision-making (SDM) has become a policy priority, yet its implementation is not routinely assessed. To address this gap we tested the delivery of CollaboRATE, a 3-item patient reported experience...

Measurement invariance across administration mode: Examining the Posttraumatic Stress Disorder (PTSD) Checklist.

The Posttraumatic Stress Disorder (PTSD) Checklist (PCL) is commonly used to screen for PTSD in clinical and research contexts. While the PCL is utilized within numerous settings and populations, research has not yet established the extent to which individuals respond similarly across different modes of administration. The use of both telephone and web survey administration modes has numerous potential benefits, including data quality improvement, but may introduce an additional source of measurement error. The current study examined the psychometric properties, including factor structure and measurement invariance, of the PCL across telephone and web administration modes among 455 wounded, ill, or injured airmen who were medically retired or undergoing evaluation for disability caused by injuries and illnesses of a physical or psychological nature. Findings suggest the properties of the PCL were invariant with regard to the mode of administration, such that the overall scale structure and size of the loadings were similar across groups. Corrections were applied to the computation of probable PTSD diagnosis to account for partial scalar invariance. The lack of complete invariance did not affect probable PTSD diagnosis. Finally, differences in latent means across the telephone and web group were nonsignificant and modest in magnitude. These results indicate that although the PCL only achieved partial scalar invariance across administration modes, the practical impact of this difference on rates of probable PTSD is negligible. The practical benefits of administering the PCL over the telephone and on the web do not appear to be outweighed by the potential cost of additional measurement error. (PsycINFO Database Record

A Reliable Method for the Evaluation of the Anaphylactoid Reaction Caused by Injectable Drugs.

Adverse reactions of injectable drugs usually occur at first administration and are closely associated with the dosage and speed of injection. This phenomenon is correlated with the anaphylactoid reaction. However, up to now, study methods based on antigen detection have still not gained wide acceptance and single physiological indicators cannot be utilized to differentiate anaphylactoid reactions from allergic reactions and inflammatory reactions. In this study, a reliable method for the evaluation of anaphylactoid reactions caused by injectable drugs was established by using multiple physiological indicators. We used compound 48/80, ovalbumin and endotoxin as the sensitization agents to induce anaphylactoid, allergic and inflammatory reactions. Different experimental animals (guinea pig and nude rat) and different modes of administration (intramuscular, intravenous and intraperitoneal injection) and different times (15 min, 30 min and 60 min) were evaluated to optimize the study protocol. The results showed that the optimal way to achieve sensitization involved treating guinea pigs with the different agents by intravenous injection for 30 min. Further, seven related humoral factors including 5-HT, SC5b-9, Bb, C4d, IL-6, C3a and histamine were detected by HPLC analysis and ELISA assay to determine their expression level. The results showed that five of them, including 5-HT, SC5b-9, Bb, C4d and IL-6, displayed significant differences between anaphylactoid, allergic and inflammatory reactions, which indicated that their combination could be used to distinguish these three reactions. Then different injectable drugs were used to verify this method and the results showed that the chosen indicators exhibited good correlation with the anaphylactoid reaction which indicated that the established method was both practical and reliable. Our research provides a feasible method for the diagnosis of the serious adverse reactions caused by injectable drugs which could be used in the clinical practice.

Comparison of the Effects of Intermittent Boluses to Simple Continuous Infusion on Patients' Global Perceived Effect in Intrathecal Therapy for Pain: A Randomized Double-Blind Crossover Study.

Intrathecal drug delivery (ITDD) is commonly used for intractable pain management. A paucity of good-quality studies in chronic noncancer patients and concerns over increased dosages have focused interest on different modes of administration. The aim of this international multicenter randomized double-blind crossover trial was to compare the efficacy of the same daily dose of drugs administered by intermittent boluses vs simple continuous infusion. Eligible patients implanted with a programmable ITDD device were randomized to receive two weeks of either intermittent boluses or a simple continuous flow in period 1, followed by a crossover to the alternative mode of administration. The primary outcome measure was the Patients' Global Impression of Change (PGIC) scale. The mean proportion of positive responders (at least "minimally improved") was 38.4% in the continuous condition vs 37.3% in the bolus (difference in proportions = 1.1%, 95% confidence interval [CI] = -21.8-24.0%, P = 0.93). The mean PGIC in the continuous condition was 3.8 vs 3.9 in the bolus (mean difference = -0.1, -0.6-0.4, P = 0.72). Exploratory analyses revealed a tendency for the mean proportion of positive responders to be higher at low vs high flow rates for both bolus and continuous administrations. Two patients were withdrawn from the study due to adverse events during the bolus phase, both with symptoms of increased pain, and one patient with additional symptoms of numbness and urinary retention. The mean PGIC and proportion of positive responders was not substantially different after intermittent bolus vs continuous administration.

Changes in oxidative stress intensity in blood of tumor-bearing rats following different modes of administration of rhenium-platinum system.

Effects of the different modes of administration of dichlorotetra-μ-isobutyratodirhenium(ІІІ) – І – (in water solution, liposomes, nanoliposomes and together with cisplatin – in the rhenium-platinum system) on the intensity of lipid peroxidation (LP) in blood plasma and the activity of the erythrocyte antioxidant enzymes were investigated on the model of tumor growth. A decrease in the concentration of TBA-active substances caused by dirhenium compounds was shown to be independent of the administration mode and the extent of the tumor growth inhibition. I was four-times more effective in inhibition of the LP burst than any known antioxidant. I induced the increasing activity of erythrocyte superoxide dismutase and decreasing activity of catalase. In vitro experiments with native superoxide dismutase, the interaction of І with following activation of the active center of the enzyme was confirmed and the superoxide dismutase activity of І was shown, that may contribute to the enhancement of the enzyme activity in vivo. The cluster rhenium compounds may be promising nontoxic potent antioxidants capable of deactivating superoxide radicals.

Comprehensive systematic review of long-term opioids in women with chronic noncancer pain and associated reproductive dysfunction (hypothalamic-pituitary-gonadal axis disruption).

A comprehensive systematic literature review of reproductive side effects in women aged 18 to 55 years treated with opioids for 1 month or longer for chronic noncancer pain. A search of 7 databases including EMBASE and Medline was undertaken (October 2014 and a limited rerun April 2016). The search contained key words for opioids (generic and specific drug names) and side effects (generic and specific reproductive). Titles were screened using predefined criteria by a single reviewer and abstracts and full texts by 2 independent reviewers. A total of 10,684 articles were identified and 12 full texts (cohort [n = 1], case-control [n = 4], cross-sectional [n = 4], case series [n = 1], and case report [n = 2] with a maximum of 41 cases in 1 article) were included covering 3 different modes of administration: oral (n = 6), intrathecal (n = 5), and transdermal (n = 1). Amenorrhoea occurred in 23% to 71% of those receiving oral or intrathecal opioids. Decreased libido was seen in 61% to 100%. Of the 10 studies that undertook hormonal assays, only 2 studies showed a statistically significant decrease in hormone levels. This review supports the view that there is a potential relationship between the use of long-term opioids in women and reproductive side effects. The evidence is however weak and the mode of administration, duration, type, and dose of opioid might influence associations. Although hormone levels were statistically significant in only 2 studies, women exhibited clinically important symptoms (decreased libido and altered menstrual cycle). Further investigation is required with larger cohorts and analysis of different delivery methods.